Evaluating higher dose of dulaglutide added to metformin for type 2 diabetes

This article investigated the safety and effectiveness of higher doses of dulaglutide (Trulicity) in the management of type 2 diabetes (T2DM) in patients on metformin (Glucophage). The authors concluded that the higher doses of dulaglutide are effective and safe in these patients.

In T2DM the body does not use insulin properly and cannot lower high blood glucose. Many treatments exist to help lower blood glucose. The first medication used is usually metformin. However, when this drug is ineffective at lowering blood glucose, other drugs are added.

Dulaglutide is a type of glucagon-like peptide-1 agonist. This increases insulin release from the pancreas which helps lower blood glucose. It also slows gastric emptying (food released from stomach after eating) which aids in weight loss. It is currently known to be effective and safe at two doses: 1.5 mg and 0.75 mg. The effectiveness and safety of higher doses of dulaglutide as an add-on to metformin are still unknown.

The study involved 318 patients with T2DM who were on metformin. They were all started on dulaglutide or a placebo. 82 patients received an injection of a placebo (no active drug). 81 received dulaglutide 1.5 mg. 79 received dulaglutide 3.0 mg and 76 received dulaglutide 4.5 mg. Patients were followed up at 18 weeks and had their HbA1c (blood test measuring blood glucose control over 3 months), body weight and fasting serum glucose (FSG; blood level of glucose while fasting) measured.

HbA1c levels were significantly reduced with dulaglutide compared to the placebo. HbA1c levels were reduced by 0.44% with placebo, by 1.23% with dulaglutide 1.5 mg, by 1.31% with dulaglutide 3.0 mg and by 1.4% with dulaglutide 4.5 mg.

Body weight was also significantly lower with dulaglutide compared to the placebo after 18 weeks. Compared to placebo, patients on dulaglutide lost an average of 1.2kg with the 1.5 mg dose, 2.4kg with the 3.0 mg dose and 2.6kg on the 4.5 mg dose. All 3 dulaglutide doses significantly reduced FSG from baseline. 

There were no significant differences between the different doses in side effects. The most common was nausea, which was dose-related (4.9% – placebo; 22.2% -1.5mg dulaglutide; 24.1% – dulaglutide 3.0mg and 30.3% – dulaglutide 4.5mg). 

The authors concluded that the higher doses of dulaglutide are effective and safe in all patients receiving it as add on therapy to metformin. 

This work was sponsored by Eli Lilly and Company, the manufacturer of dulaglutide. This was a Phase 2 study. Larger studies are needed.